The purpose of this study is to determine whether or not XL184 demonstrates anti-tumor activity in selected tumor types under a randomized discontinuation trial (RDT) design. Subjects who have responded to study drug after 12 weeks of open-label XL184 administration will continue to take XL184. Subjects who are clearly progressing will discontinue study treatment and subjects who demonstrate stable disease will be randomized to either XL184 or placebo. For individual patients, once disease progression is observed, the blind will be broken and subjects who were randomized to placebo will be offered the option to receive open-label XL184. Subjects who progressed while taking XL184 will discontinue study treatment.

Emerging data may support enrollment in an open-label, non-randomized expansion cohort (NRE). There will be NRE cohorts for prostate and ovarian cancers.

To evaluate the efficacy of XL184 in subjects with advanced solid tumors [ Time Frame: Assessed approximately every 6 weeks using MRI, CT, and/or bone scans ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability of XL184 in subjects with advanced solid tumors [ Time Frame: Assessed approximately every 3 weeks, during study visits ] [ Designated as safety issue: Yes ]

To correlate the pathway dysfunction of disease-related genes or proteins such as MET and downstream signaling molecules with clinical outcome [ Time Frame: Assessed approximately every 6 weeks through blood samples and tumor biopsies ] [ Designated as safety issue: No ]

To further characterize the pharmacokinetic (PK) and pharmacodynamic parameters of XL184 [ Time Frame: Assessed approximately every 6 weeks through blood samples ] [ Designated as safety issue: No ]

After 12 weeks of open-label daily XL184, subjects with stable disease randomized to Arm 3 will receive capsules of placebo that are size- and color-matched to XL184 administered daily until disease progression. Subjects will be unblinded at disease progression and, if found to be receiving placebo, given the option to receive XL184.

The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below:

Pancreatic Cancer

Castration-Resistant Prostate Cancer (CRPC)

Hepatocellular Carcinoma (HCC)

Gastric or Gastroesophageal Junction Cancer

Melanoma

Small Cell Lung Cancer (SCLC)

Ovarian cancer, primary peritoneal or fallopian tube carcinoma

Breast cancer that is one of the following subtypes: estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative), or inflammatory (regardless of receptor status) disease histology

Non-Small Cell Lung Cancer (NSCLC)

Certain requirements for prior therapies may apply

The subject has documented progressive disease at screening

Subjects having any tumor type of other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan

The subject has recovered to baseline or CTCAE ≤ Grade 1 from toxicities related to prior treatment (some exceptions apply)

The subject is ≥ 18 years old on the day of consent

Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor

The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

The subject has adequate organ function

The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document

Sexually active fertile subjects (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug(s)

Female subjects of childbearing potential must have a negative pregnancy test at screening

Exclusion Criteria:

The subject has experienced clinically-significant hematemesis or hemoptysis of >0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment

The subject has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel

Certain restrictions on prior treatments apply

The subject has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment

The subject has known symptomatic or uncontrolled brain metastases or epidural disease

The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation

The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00940225